Dimension Engineering of Stimuli-Responsive 1D Molecular Crystals into Unusual 2D and 3D Zigzag Waveguides.

We demonstrate an innovative technique to achieve organic 2D and 3D waveguides with peculiar shapes from an acicular, stimuli-responsive molecular crystal, (2Z,2'Z)-3,3'-(anthracene-9,10-diyl)bis(2-(3,5-bis(trifluoromethyl)phenylacrylonitrile), Ant-CF3 . The greenish-yellow fluorescent (FL) Ant-CF3 molecular crystals exhibit laser power-dependent permanent mechanical bending in 2D and 3D. Investigation of a single-crystal using spatially-resolved Raman/FL/electron microscopy, and theoretical calculations revealed photothermal (Z,E)/(E,E) isomerization-assisted transition from crystalline to amorphous phase at the laser-exposed regions. This phenomenon facilitates the dimension engineering of a 1D crystal waveguide into 2D waveguide on a substrate or a 3D waveguide in free space. The bends can be used as interconnection points to couple different optical elements. The presented technique has broader implications in organic photonics and other crystal-related photonic technologies.

1,2-Phenylene-Incorporated Smallest Expanded Calix[4]pyrrole via One-Step Synthesis of Tetrapyrrane: A Fluorescent Host for Fluoride Ion.

Synthesis of tetrapyrrane 8 from acetone and pyrrole via one-step condensation was achieved for the first time along with a much-improved yield of the tripyrrane 9. Diborylation of the tetrapyrrane and subsequent "1 + 1" cyclocoupling with 1,2-diiodobenzene following the Suzuki protocol generated novel o-phenylene incorporated macrocycle belonging to the smallest meso-expanded calix[4]pyrrole family. The latter macrocycle displays exclusive turn-on fluorescence sensing of fluoride ion upon complexation via a unique partial cone conformation supported by DFT analysis in acetonitrile solvent.

Assessment of Fragmentation Strategies for Large Proteins Using the Multilayer Molecules-in-Molecules Approach.

We present a rigorous evaluation of the potential for the multilayer Molecules-in-Molecules (MIM) fragmentation method to be applied to large biomolecules. Density functional total energies of a test set of 8 peptides, sizes ranging from 107 to 721 atoms, were evaluated with MIM and compared to unfragmented energies to help develop a protocol for the treatment of large proteins. Fragmentation schemes involving subsystems of 4 to 5 covalently bonded fragments (tetramer or pentamer schemes) were tested with a single level of theory (MIM1) and produced errors on the order of 100 kcal/mol due to the relatively small size of the subsystems and the neglect of nonbonded interactions. Supplementing the two schemes with nonbonded dimer subsystems, formed from fragments within a specified cutoff distance (3.0 Å), nearly cut the MIM1 errors in half, leading us to employ these new schemes as starting points in multilayer calculations. When employing a DFT low level with a substantially smaller basis set (MIM2), the dimer-supplemented schemes produce errors below our target accuracy of 2 kcal/mol in the majority of cases. However, for the larger test systems, such as the 45 residue slice of a human protein kinase with over 10,000 basis functions in the high level, the low level calculation over the full molecule becomes the bottleneck for MIM2 calculations. To overcome any associated limitations, we explored, for the first time, 3-layer MIM methods (MIM3) with a distance-based medium level of fragmentation and dispersion-corrected semiempirical methods (e.g., PM6-D3) as the low level. A modestly sized cutoff distance in the medium level (3.0-3.5 Å), leading to subsystems of 30-50 atoms treated at the medium and low levels of theory, was able to match the low errors of the MIM2 calculations. These results allow us to develop a general prescription for 3-layer calculations wherein a much cheaper low level can be used, while fragment sizes in the high layer stay modest, allowing the MIM method to be applied to very large proteins in the future.

Cooperative Formation of Icosahedral Proline Clusters from Dimers.

Ion mobility spectrometry-mass spectrometry and Fourier transform infrared spectroscopy (FTIR) techniques were combined with quantum chemical calculations to examine the origin of icosahedral clusters of the amino acid proline. When enantiopure proline solutions are electrosprayed (using nanospray) from 100 mM ammonium acetate, only three peaks are observed in the mass spectrum across a concentration range of five orders of magnitude: a monomer [Pro+H]+ species, favored from 0.001 to 0.01 mM proline concentrations; a dimer [2Pro+H]+ species, the most abundant species for proline concentrations above 0.01 mM; and, the dimer and dodecamer [12Pro+2H]2+ for 1.0 mM and more concentrated proline solutions. Electrospraying racemic D/L-proline solutions from 100 mM ammonium acetate leads to a monomer at low proline concentrations (0.001 to 0.1 mM), and a dimer at higher concentrations (>0.09 mM), as well as a very small population of 8 to 15 Pro clusters that comprise <0.1% of the total ion signals even at the highest proline concentration. Solution FTIR studies show unique features that increase in intensity in the enantiopure proline solutions, consistent with clustering, presumably from the icosahedral geometry in bulk solution. When normalized for the total proline, these results are indicative of a cooperative formation of the enantiopure 12Pro species from 2Pro. Graphical Abstract.

Raman Optical Activity Spectra for Large Molecules through Molecules-in-Molecules Fragment-Based Approach.

We present an efficient method for the calculation of the Raman optical activity (ROA) spectra for large molecules through the molecules-in-molecules (MIM) fragment-based method. The relevant higher energy derivatives from smaller fragments are used to build the property tensors of the parent molecule to enable the extension of the MIM method for evaluating ROA spectra (MIM-ROA). Two factors were found to be particularly important in yielding accurate results. First, the link-atom tensor components are projected back onto the corresponding host and supporting atoms through the Jacobian projection method, yielding a mathematically rigorous method. Second, the long-range interactions between fragments are taken into account by using a less computationally expensive lower level of theory. The performance of the MIM-ROA model is calibrated on the enantiomeric pairs of 10 carbohydrate benchmark molecules, with strong intramolecular interactions. The vibrational frequencies and ROA intensities are accurately reproduced relative to the full, unfragmented, results for these systems. In addition, the MIM-ROA method is employed to predict the ROA spectra of d-maltose, α-D-cyclodextrin, and cryptophane-A, yielding spectra in excellent agreement with experiment. The accuracy and performance of the benchmark systems validate the MIM-ROA model for exploring ROA spectra of large molecules.

Electrostatic Potential-Based Method of Balancing Charge Transfer Across ONIOM QM:QM Boundaries.

The inability to describe charge redistribution effects between different regions in a large molecule can be a source of error in an ONIOM hybrid calculation. We propose a new and an inexpensive method for describing such charge-transfer effects and for improving reaction energies obtained with the ONIOM method. Our method is based on matching the electrostatic potential (ESP) between the model system and the real system. The ESP difference arising due to charge redistribution is overcome by placing an optimum one electron potential at a defined buffer region. In our current implementation, the link atom nuclear charge is optimized iteratively to produce a model low ESP distribution equal to that in the real low calculation. These optimum charges are relatively small in magnitude and corroborate physical intuition. This new ESP-ONIOM-CT method is independent of any arbitrary definition of charges, is defined on the basis of a physical observable, and is less basis set dependent than previous approaches. The method is easily extended for studying reactions involving multiple link atoms. We present a thorough benchmark of this method on test sets consisting of one- and two-link atom reactions. Using reaction energies of four different test sets each with four different combinations of high:low levels of theory, the accuracy of ESP-ONIOM-CT improved by 40-60% over the ONIOM method.